“The name change is our way of emphasizing the greater sensitivity of the assay and its value in helping identify individuals at risk of cardiovascular disease or cardiac events,” explains Monica Rassai, Beckman Coulter Marketing Product Manager. “The new name will also underscore the change in the assay’s intended use to include cardiac risk assessment and risk stratification.”
A New Claim
With the new cardiac claim, the hsCRP assay can be used as an independent risk marker to help identify individuals at risk for future cardiovascular disease or cardiac events, such
as myocardial infarction.
“These changes can mean big benefits for clinical labs that currently run the assay on SYNCHRON LX® PRO systems , UniCel® DxC 600/800 systems and IMMAGE® 800 systems and will provide more options to manage and evaluate cardiovascular disease better and improve patient management,” says Rassai.
Other Technical Features
Once cleared by the U.S. Food and Drug Administration (FDA), the new hsCRP assay will have a new part number for the IMMAGE 800 assay kit, but the part number for the SYNCHRON assay will remain the same.
According to Dan Seymour, Beckman Coulter Group Project Manager, Chemistry Development, one of the primary benefits of the high sensitivity CRP assay is its large dynamic range. When used on the SYNCHRON platform, it has a 400-fold measuring range that can not only measure normal, chronic or acute inflammation, but also measure the low-level cardiac range.
“This enables labs to use one product for multiple needs, instead of purchasing and stocking multiple assays,” explains Seymour. “Plus, because of the large measuring range, the system doesn’t have to perform multiple dilutions or reflex testing as often.”
The Recent Growth of Cardiac Risk Markers
For more than 20 years, coronary heart disease and stroke have been the first and third leading causes of death and major causes of disability in the United States and other developed countries, according to the World Health Organization. And according to the American Heart Association (AHA), cardiovascular disease remains the number one cause of death in the United States, outranking all cancers by more than 60 percent.
Thus, the search for biomarkers that can better detect coronary patients who could potentially benefit from intensive prevention efforts is critically important. Thanks to a rapidly growing research base, the number of potential predictors of cardiovascular disease has grown considerably.
One of those potentially useful cardiac predictors is CRP. High sensitivity CRP assays have significantly lower limits of detection than conventional CRP and functional sensitivities that may be used to support new clinical uses of CRP quantitation. When used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, CRP values may be useful as independent markers of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndromes.
Clinical Significance of CRP
Blood levels of CRP are known to rise rapidly from normal baseline levels of <0.3 mg/dL to as high as 50 mg/dL or 0.03mg/L to 5.0 mg/L as part of the body’s non-specific inflammatory response to infection or injury. 1,2,3,4,5,6 In more recent years, the utility of measuring high sensitivity CRP has expanded from its historical use as a sensitive marker of acute inflammation to include assessment of cardiac events and risk.
For example, some studies have shown that people who have hsCRP results in the high end of the normal range have 1.5 to 4 times the risk of having a heart attack as those with CRP values at the low end of the normal range.
Higher CRP levels, however, are simply a reflection of higher than normal inflammation—but cannot indicate the source of the inflammation. Heightened CRP levels could be caused by a fever or may come from cells in the fatty deposits in arterial walls that reflect the process of atherosclerosis, the chief underlying cause of myocardial infarction.
For this reason, hsCRP is usually ordered as one of several tests in a cardiovascular risk profile, often along with tests for cholesterol and triglycerides. In fact, some experts say the best way to predict risk is to combine a good marker for inflammation, like CRP, along with the ratio of total cholesterol to HDL cholesterol.
Current Recommendations
To help clarify when CRP testing may be most useful, the AHA and Centers for Disease Control and Prevention (CDC) examined current evidence and then published their recommendations for its use in the 2006 National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines: Emerging Biomarkers of Cardiovascular Disease and Stroke, which can be viewed at
http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/DraftGuidelines/Emerg_Risk_Factors
The consensus was that CRP:
- Should not be used for widespread screening of the general adult population, but rather, physicians should continue focusing on major risk factors, such as high blood pressure, high cholesterol, smoking and diabetes.
- In patients with stable coronary disease or acute coronary syndromes, hsCRP measurement may be useful as an independent marker for assessing likelihood of recurrent events, including death, myocardial infarction or restenosis after percutaneous coronary intervention.
- Is useful as an independent marker of risk and as a “discretionary tool” in the evaluation of those with moderate risk of cardiovascular disease to help determine a course of treatment.
- Should not be used for tracking treatment efficacy due to lack of evidence that reducing CRP levels improves outcomes, such as survival.
Cardiovascular Risk Classification
The AHA and CDC defined three risk groups as follows:
Risk Level |
CRP (mg/L) |
CRP (mg/dL) |
| Low |
<1.0 |
<0.10 |
| Average |
1.0 - 3.0 |
0.10 –
0.30 |
| High |
>3.0 |
>0.30 |
Three Types of CRP Assays
Conventional CRP
Conventional CRP assays are used to evaluate infection, tissue injury and inflammatory disorders. Test values are typically considered to be clinically significant at levels above 1.0 mg/dL (10 mg/L).
High Sensitivity CRP
These assays have a measurement range that extends below the range of most conventional CRP assays. This lower range of measurement may expand the indications for use to include the evaluation of conditions thought to be associated with inflammation in otherwise healthy individuals. Increases in hsCRP values are general and not associated with specific diseases or risks for disease
Cardiac CRP
Cardiac CRP assays, like high sensitivity CRP assays, have measurement ranges that extend below that which is typical for most conventional CRP assays. The difference between hsCRP and cardiac CRP is not the analyte itself, but is due to the additional performance validation to support the expanded intended use in the evaluation of coronary disease.
Conclusion
If your lab has been anticipating using Beckman Coulter’s high sensitivity CRP for cardiac risk stratification, your wait is almost over. In the coming months, please watch for a product announcement letter providing details about this new development.
If you’d like to receive additional information or a chemistry information sheet, please contact your Beckman Coulter sales representative.
References
1. Pepys, M. B., et al., C-Reactive Protein Fifty Years On, Lancet, 21:653 (1981).
2. Pepys, M. B., Baltz, M. L., “Acute Phase Proteins With Special Reference to C-Reactive Protein and Related Proteins (Pentraxins) and Serum Amyloid A Protein”, Adv. Immunol., 34:141 (1983).
3.
Eur. J. Clin. Chem. Clin. Biochem.
4. Ballicre’s Clinical Rheumatology., 8:513 530 (1994).
5.
Int. Med., 5:112 151 (1984).
6.
Textbook of Clinical Chemistry, 3rd Edition, W. B. Saunders, Philadelphia, PA (1999) |
